Elevated Serum Cystatin C and Decreased Cathepsin S/Cystatin C Ratio Are Associated with Severe Peripheral Arterial Disease and Polyvascular Involvement.

Peripheral arterial disease (PAD) is frequently associated with atherosclerotic manifestations of the carotids and coronaries. Polyvascular involvement and low ankle−brachial index predict major cardiovascular events and high mortality. Cathepsin S (Cat S) promotes the inflammatory pathways of the arterial wall, while Cystatin C (Cys C) functions as its inhibitor; therefore, Cys C was proposed to be a biomarker of progression in PAD. In a single-center observational study, we investigated the correlations of serum Cys C and Cat S/Cys C ratio in a group of 90 PAD patients, predominantly with polyvascular involvement. Cys C and Cat S/Cys C were associated with ankle−brachial index (ABI) scores <0.4 in univariate and multiple regression models. Furthermore, both markers correlated positively with the plasma Von Willebrand Factor Antigen (VWF: Ag) and Von Willebrand Factor collagen-binding activity (VWF: CB). In addition, Cat S/Cys C was significantly decreased, whereas Cys C increased in subjects with three-bed atherosclerotic involvement. According to our results, high serum Cys C and low Cat S/Cys C ratios may indicate severe peripheral arterial disease and polyvascular atherosclerotic involvement.

The Post-thrombotic Syndrome-Prevention and Treatment: VAS-European Independent Foundation in Angiology/Vascular Medicine Position Paper.

Importance: The post-thrombotic syndrome (PTS) is the most common long-term complication of deep vein thrombosis (DVT), occurring in up to 40-50% of cases. There are limited evidence-based approaches for PTS clinical management. Objective: To provide an expert consensus for PTS diagnosis, prevention, and treatment. Evidence-Review: MEDLINE, Cochrane Database review, and GOOGLE SCHOLAR were searched with the terms "post-thrombotic syndrome" and "post-phlebitic syndrome" used in titles and abstracts up to September 2020. Filters Were: English, Controlled Clinical Trial / Systematic Review / Meta-Analysis / Guideline. The relevant literature regarding PTS diagnosis, prevention and treatment was reviewed and summarized by the evidence synthesis team. On the basis of this review, a panel of 15 practicing angiology/vascular medicine specialists assessed the appropriateness of several items regarding PTS management on a Likert-9 point scale, according to the RAND/UCLA method, with a two-round modified Delphi method. Findings: The panelists rated the following as appropriate for diagnosis: 1-the Villalta scale; 2- pre-existing venous insufficiency evaluation; 3-assessment 3-6 months after diagnosis of iliofemoral or femoro-popliteal DVT, and afterwards periodically, according to a personalized schedule depending on the presence or absence of clinically relevant PTS. The items rated as appropriate for symptom relief and prevention were: 1- graduated compression stockings (GCS) or elastic bandages for symptomatic relief in acute DVT, either iliofemoral, popliteal or calf; 2-thigh-length GCS (30-40 mmHg at the ankle) after ilio-femoral DVT; 3- knee-length GCS (30-40 mmHg at the ankle) after popliteal DVT; 4-GCS for different length of times according to the severity of periodically assessed PTS; 5-catheter-directed thrombolysis, with or without mechanical thrombectomy, in patients with iliofemoral obstruction, severe symptoms, and low risk of bleeding. The items rated as appropriate for treatment were: 1- thigh-length GCS (30-40 mmHg at the ankle) after iliofemoral DVT; 2-compression therapy for ulcer treatment; 3- exercise training. The role of endovascular treatment (angioplasty and/or stenting) was rated as uncertain, but it could be considered for severe PTS only in case of stenosis or occlusion above the inguinal ligament, followed by oral anticoagulation. Conclusions and Relevance: This position paper can help practicing clinicians in PTS management.

MPFF 1000 mg chewable once daily vs. MPFF 500 mg twice daily in chronic venous disease: the double-blind, randomized, non-inferiority CHEWY trial.

BACKGROUND: The efficacy and tolerability of the new micronized purified flavonoid fraction (MPFF) 1000 mg once-daily chewable formulation in comparison with the established MPFF 500 mg conventional tablet at the same daily dose are unknown. METHODS: CHEWY was an international, multicenter, double-blind, double-dummy, randomized, parallel group, non-inferiority phase III study conducted in adult patients with symptomatic chronic venous disease (CVD). Patients were randomly allocated to MPFF 1000 mg chewable or MPFF 2x500 mg daily treatment. The primary efficacy endpoint for clinical non-inferiority (non-inferiority margin predefined at 1 cm) was lower limb discomfort (LLD) assessed by a 10 cm electronic visual analog scale (eVAS) at 8 weeks. Secondary endpoints included leg pain (LP), leg heaviness (LH), and quality of life (QoL) measured by the eCIVIQ-14 questionnaire. Overall acceptability was assessed at each visit by patient and investigator. RESULTS: Three hundred and nine patients were randomized to MPFF 1000 mg chewable and 302 to MPFF 2x500 mg. After 8 weeks, LLD decreased from baseline by -3.6±2.4 cm and -3.6±2.5 cm in the MPFF chewable and 2x500 mg groups, respectively. Non-inferiority of the once-daily chewable formulation compared with twice daily tablets on improving LLD was demonstrated (adjusted between-group difference [Standard Error]) (E [SE]) = 0.00 (0.18) cm, 95%CI -0.35; 0.35, non-inferiority P value <0.0001. Decreases of similar magnitude were observed at 8 weeks for LP and LH in both treatment arms: -3.4±2.3 cm and -3.5±2.5 cm, respectively for LP, and -3.5±2.5 cm and -3.5±2.6 cm, respectively for LH. QoL (global score) improved by -21.0±17.2 and -22.5±20.1 in the MPFF 1000 mg chewable group and 2x500 mg groups, respectively (E [SE]=1.03 [1.20], 95%CI [-1.32; 3.38]), with similar improvements in the QoL subscore components in both groups. Treatment acceptability was high for both patients and physicians and tolerability similar to the tablet formulation. CONCLUSIONS: MPFF 1000 mg chewable was non-inferior to MPFF 2x500 mg tablets with respect to its effect on LLD. Both formulations were associated with improvements of similar magnitude in lower limb symptoms and QoL. The chewable formulation was observed to be well tolerated and well accepted. Once-daily MPFF chewable tablet offers patients with CVD a good alternative treatment regimen.

May-Thurner syndrome - Are we aware enough?

Iliac vein compression syndrome (May-Thurner syndrome - MTS) is an anatomically variable clinical condition in which the left common iliac vein is compressed between the right common iliac artery and the underlying spine. This anatomic variant results in an increased incidence of left iliac or iliofemoral vein thrombosis. It predominantly affects young women in the second or third decades of life with preponderance during pregnancy or oral contraceptive use. Although MTS is rare, its true prevalence is underestimated but it can be a life-threatening condition due to development of pulmonary embolism (PE). In this case based review the authors present three cases of MTS. All patients had been previously confirmed with PE, but despite they were admitted to hospital, diagnosed and correctly treated for PE and investigated for thrombophilia, the iliac vein compression syndrome was not suspected or investigated. With this presentation the authors would like to emphasize that MTS is mostly underdiagnosed, and it needs to be ruled out in left iliofemoral vein thrombosis in young individuals.

High circulating osteoprotegerin levels are associated with non-zero blood groups.

BACKGROUND: Osteoprotegerin (OPG) and von Willebrand factor (VWF) form complex within endothelial cells and following secretion. The nature of blood group antigens strongly influences the levels of circulating VWF, but there is no available data concerning its ascendancy on OPG levels. We aimed to assess the relationship of AB0 blood groups with OPG, VWF levels (VWF: Ag) and collagen binding activity (VWF: CB) in peripheral arterial disease (PAD) patients. METHODS: Functional and laboratory parameters of 105 PAD patients and 109 controls were examined. Results of OPG, VWF: Ag, VWF: CB (ELISA-s) were analysed by comparative statistics, together with clinical data. RESULTS: OPG levels were higher in patients than in controls (4.64 ng/mL vs. 3.68 ng/mL, p < 0.001). Among patients elevation was marked in the presence of critical limb ischemia (5.19 ng/mL vs. 4.20 ng/mL, p = 0.011). The OPG in patients correlated positively with VWF: Ag and VWF: CB (r = 0.26, p = 0.008; r = 0.33, p = 0.001) and negatively with ankle-brachial pressure index (r = -0.22, p = 0.023). Furthermore, OPG was significantly elevated in non-0 blood groups compared to 0-groups both in patients and controls (4.95 ng/mL vs. 3.90 ng/mL, p = 0.012 and 4.09 ng/mL vs. 3.40 ng/mL, p = 0.002). CONCLUSIONS: OPG levels are associated to blood group phenotypes and higher in non-0 individuals. Increased OPG levels in PAD characterize disease severity. The significant correlation between OPG and VWF:CB might have functional importance in an atherothrombosis-prone biological environment.